Devices, systems, and methods to determine fractional flow reserve

ABSTRACT

Devices, systems, and methods to determine fractional flow reserve. At least one method for determining fractional flow reserve of the present disclosure comprises the steps positioning a device comprising at least two sensors within a luminal organ at or near a stenosis, wherein the at least two sensors are separated a predetermined distance from one another, operating the device to determine flow velocity of a second fluid introduced into me luminal organ to temporarily displace a first fluid present within the luminal organ, and determining fractional flow reserve at or near the stenosis based upon the flow velocity, a mean aortic pressure within the luminal organ, and at least one cross-sectional area at or near the stenosis. Devices and systems useful for performing such exemplary methods are also disclosed herein.

PRIORITY

The present application is related to, claims the priority benefit of,and is a U.S. continuation patent application of, U.S. patentapplication Ser. No. 13/120,308, filed Mar. 22, 2011 and issued as U.S.Pat. No. 8,702,613 on Apr. 22, 2014, which is related to, claims thepriority benefit of, and is a U.S. national stage application of,International Patent Application Serial No. PCT/US2009/057800, filedSep. 22, 2009, which is related to, and claims the priority benefit of,U.S. Provisional Patent Application Ser. No. 61/098,837, filed Sep. 22,2008. The contents of each of these applications and patent are herebyincorporated by reference in their entirety into this disclosure.

BACKGROUND

Coronary heart disease remains the leading cause of morbidity andmortality in the United States and the developed world. Although thecurrent “gold standard” for assessing coronary artery disease (CAD) isangiography, it has serious limitations in evaluating the functionalsignificance of intermediate coronary lesions (comprising 30-70%stenosis). Coronary angiography relies on a visual interpretation ofcoronary anatomy. A number of studies have documented the large intra-and inter-observer variability that results from visual grading ofcoronary stenotic lesions. Moreover, studies have shown a lack ofcorrelation between the angiographic delineated stenosis with theirphysiologic severity on coronary flow. This stems from the highlynon-linear relation between the degree of stenosis and the change inblood flow. Typically, the blood flow remains unchanged until the degreeof stenosis reaches a critical range (typically >80%), at which pointthe decrease in flow is quite dramatic. Lesions that are notfunctionally significant (i.e., do not reduce the flow) may not needtreatment. Hence, there is a need for complementary methods toconventional coronary arteriograms that combine coronary anatomy andphysiology to assess CAD accurately.

Blood vessel diameter or cross-sectional area gives anatomic measures ofstenosis severity. Coronary blood flow, on the other hand, reflectscoronary hemodynamic function and can be used to assess functionalseverity of stenosis through parameters such as coronary flow reserve(CFR) and fractional flow reserve (FFR). CFR, defined as the ratio ofhyperemic (induced by pharmacological agents) to resting flow in acoronary artery. It has been previously found that a significantstenosis leading to inducible ischemia occurs when CFR has a value lessthan 2.0. Normally, the coronary circulation has a flow reserve of 3-5times that of normal resting blood flow. This reserve stems from thetone of small blood vessels (microvascular bed). In disease, themicrovascular bed dilates and uses some of its reserve to compensate forthe pressure drop to the stenosis. Hence, a low CFR value cancharacterize disease in the epicardial arteries or the distal resistivemicrovascular bed.

CFR can be estimated from hyperemic and resting blood velocitiesmeasured by a Doppler guidewire. This method is based on the principleof Doppler which requires that the piezo-electric crystal to be at aspecific angle to the flowing blood. Since this condition is verydifficult to meet in clinical practice as the tip of the wire isdifficult to align with the direction of flow, the measurements are notreliably accurate and this method has not enjoyed clinical utility.Recent developments have introduced methods and systems for accuratedetermination of cross-sectional area of blood vessels includingcoronary arteries. Simultaneous measurements of cross-sectional area andflow (including CFR) would provide a clinician with a greater insight inthe contribution of the epicardial vessel and microvasculature to totalresistance to myocardial blood flow.

In summary, there are well-known limitations to the use of visualestimation to assess the severity of coronary artery disease and luminalstenosis. This is especially true in the case of intermediate coronarylesion where coronary angiography is very limited in distinguishingischemia-producing intermediate coronary lesions fromnon-ischemia-producing ones. For this reason, a functional measure ofstenosis severity is desirable. Previous devices involving Doppler flowwires also have serious limitations as referenced above. Hence, there isclearly a need for a simple, accurate, cost effective solution todetermination of coronary blood flow in routine practice.

BRIEF SUMMARY

in at least one embodiment of a method for determining fractional flowreserve within a luminal organ of the present disclosure, the methodcomprises the steps of positioning a device comprising at least twosensors within a luminal organ at or near a stenosis, wherein the atleast two sensors are separated a predetermined distance from oneanother, operating the device to determine flow velocity of a secondfluid introduced into the luminal organ to temporarily displace a firstfluid present within the luminal organ, and determining fractional flowreserve at or near the stenosis based upon the flow velocity, a meanaortic pressure within the luminal organ, and at least onecross-sectional area at or near the stenosis. In at least oneembodiment, the at least one cross-sectional area comprises across-sectional area of the luminal organ distal to the stenosis, across-sectional area of the luminal organ proximal to the stenosis, andat least one cross-sectional area of the luminal organ at the stenosis.

In another exemplary embodiment of a method for determining fractionalflow reserve within a luminal organ of the present disclosure, the stepof determining fractional flow reserve is further based upon adetermination of volumetric flow between the at least two sensors. In anadditional embodiment, the determination of volumetric flow is basedupon the flow velocity and the at least one cross-sectional area.

In an exemplary embodiment of a method for determining fractional flowreserve within a luminal organ of the present disclosure, the step ofoperating the device to determine flow velocity of a fluid introducedinto the luminal organ comprises the steps of detecting the first fluidwithin the luminal organ using at least one of the at least two sensors,wherein the first fluid has a first parameter having a first value,introducing the second fluid into the luminal organ, said second fluidtemporarily displacing the first fluid within the luminal organ at thesite of introduction, wherein the second fluid has a second paramaterhaving a second value, the second value differing from the first value,detecting the second value of the second parameter of the second fluidby the at least two sensors, measuring time of detection of the secondvalue of the second parameter of the second fluid by each of the atleast two sensors, and determining flow velocity of the second fluidwithin the luminal organ based upon the time of detection of the secondvalue of the second parameter of the second fluid by each of the atleast two sensors. In at least one embodiment, the first parameter andthe second parameter are conductivity, pH, temperature, or anoptically-detectable substance. In another exemplary embodiment, themethod further comprises the step of diagnosing a disease based upon thedetermination of flow velocity within a luminal organ. In yet anotherembodiment, the determination of fractional flow reserve is indicativeof a degree of stenosis within the lumina organ. In an exemplaryembodiment, the step of determining fractional flow reserve is performedusing a data acquisition and processing system. In at least oneembodiment, the first fluid comprises blood and the second fluidcomprises saline.

In at least one embodiment of a method for determining fractional flowreserve within a luminal organ of the present disclosure, the method isbawd upon at least the detection of an introduced bolus within a luminalorgan, wherein the introduced bolus has a parameter with a valuedifferent from the value of the parameter of the fluid present withinthe luminal organ prior to the introduction of the bolus.

In at least one embodiment of a method for determining fractional flowreserve within a luminal organ using impedance of the presentdisclosure, the method comprises the steps of positioning a devicecomprising a pair of excitation electrodes and at least two pairs ofdetection electrodes within a luminal organ at or near a stenosis,wherein the at least two pairs of detection electrodes are separated apredetermined distance from each other, operating the device todetermine flow velocity of a second fluid introduced into the luminalorgan, said second fluid temporarily displacing a first fluid presentwithin the luminal organ, and determining fractional flow reserve at ornear the stenosis based upon the flow velocity, a mean aortic pressurewithin the luminal organ, and at least one cross-sectional area at ornear the stenosis. In at least one embodiment, the at least onecross-sectional area comprises a cross-sectional area of the luminalorgan distal to the stenosis, a cross-sectional area of the luminalorgan proximal to the stenosis, and at least one cross-sectional area ofthe luminal organ at the stenosis.

In at least one embodiment of a method for determining fractional flowreserve within a luminal organ using impedance of the presentdisclosure, the step of determining fractional flow reserve is furtherbased upon a determination of volumetric flow between the at least twopairs of detection electrodes. In another embodiment, the determinationof volumetric flow is based upon the flow velocity and the at least onecross-sectional area.

In at least one embodiment of a method for determining fractional flowreserve within a luminal organ using impedance of the presentdisclosure, the step of operating the device to determine flow velocityof a fluid introduced into the luminal organ comprises the steps ofactivating the pair of excitation electrodes to generate a fielddetectable by the detection electrodes, detecting conductance of thefirst fluid having a first conductivity within the luminal organ usingat least one pair of the at least two pairs of detection electrodes,introducing the second fluid having a second conductivity into theluminal organ, said second fluid temporarily displacing the first fluidwithin the luminal organ at the site of introduction, wherein the firstconductivity does not equal the second conductivity, detecting theconductance of the second fluid by the at least two pairs of detectionelectrodes, measuring time of conductance detection of the second fluidby each of the at least two pairs of detection electrodes, anddetermining flow velocity of the second fluid within the luminal organbased upon the time of conductance detection by each of the at least twopairs of detection electrodes.

In at least one embodiment of a method for determining fractional flowreserve within a luminal organ using impedance of the presentdisclosure, the step of operating the device to determine flow velocityof a fluid introduced into the luminal organ comprises the steps ofactivating the pair of excitation electrodes to generate a field,detecting conductance of the first fluid having a first conductivitywithin the luminal organ using at least one pair of the at least twopairs of detection electrodes, introducing the second fluid having asecond conductivity into the luminal organ, said second fluidtemporarily displacing the first fluid within the luminal organ at thesite of introduction, wherein the first conductivity does not equal thesecond conductivity, detecting the conductance of the second fluid bythe at least two pairs of detection electrodes, measuring time ofconductance detection of the second fluid using at least one pair of theat least two pairs of detection electrodes, and determining flowvelocity of the second fluid within the luminal organ based upon thetime of conductance detection using (a) a first excitation electrode ofthe pair of excitation electodes and a first pair of detectionelectrodes of the at least two pairs of detection electrodes, and (b) asecond excitation electrode of the pair of excitation electodes and asecond pair of detection electrodes of the at least two pairs ofdetection electrodes.

In at least one embodiment of a method for determining fractional flowreserve within a luminal organ using impedance of the presentdisclosure, the method further comprises the step of diagnosing adisease based upon the determination of flow velocity within a luminalorgan. In another embodiment, the determination of fractional flowreserve is indicative of a degree of stenosis within the luminal organ.In yet another embodiment, the step of determining fractional flowreserve is performed using a data acquisition and processing system. Inat least one exemplary embodiment, the first fluid comprises blood andthe second fluid comprises saline.

In at least one embodiment of a method for determining fractional flowreserve within a luminal organ using impedance of the presentdisclosure, the method is based upon at least the detection of anintroduced bolus within a luminal organ, wherein the introduced bolushas a conductivity different from the conductivity of the fluid presentwithin the luminal organ prior to the introduction of the bolus.

In at least one embodiment of a device for determining fractional flowreserve of a fluid within a luminal organ of the present disclosure, thedevice comprises an elogated body sized and shaped to fit within aluminal organ, and at least two sensors positioned along the elongatedbody a predetermined distance from one another, wherein the device isoperable to detect a first fluid with a first parameter having a firstvalue using at least one of the at least two sensors when the device ispositioned within the luminal organ, and wherein the device is furtheroperable to detect a second fluid having a second parameter, wherein thesecond parameter of the second fluid has a second value different fromthe first value, upon introduction of the second fluid within theluminal organ at or near the at least two sensors. In at least oneembodiment, the second fluid detected by the at least two sensors allowsfor the determination of flow velocity based upon timing of the detectedsecond fluid by the at least two sensors and the distance between the atleast two sensors. In another embodiment, the device is further operableto determine fractional flow reserve when the device is positionedwithin the luminal organ at or near a stenosis, wherein the fractionalflow reserve is based upon the flow velocity, a mean aortic pressurewithin the luminal organ, and at least one cross-sectional area at ornear the stenosis. In yet another embodiment, the at least onecross-sectional area comprises a cross-sectional area of the luminalorgan distal to the stenosis, a cross-sectional area of the luminalorgan proximal to the stenosis, and at least one cross-sectional area ofthe luminal organ at the stenosis.

In at least one embodiment of a device for determining fractional flowreserve of a fluid within a luminal organ of the present disclosure, theflow velocity allows for the determination of volumetric flow based uponthe flow velocity and a cross-sectional area of the luminal organ. Inanother embodiment, the determination of fractional flow reserve is madeusing a data acquisition and processing system.

In at least one embodiment of a device for determining fractional flowreserve of a fluid within a luminal organ of the present disclosure, thedevice comprises an elogated body sized and shaped to fit within aluminal organ, at least one pair of excitation electrodes positionedalong the elongated body, and at least two pairs of detection electrodespositioned along the elongated body between the at least one pair ofexcitation electrodes, wherein the at least two pairs of detectionelectrodes are positioned a predetermined distance from each other,wherein when the device is positioned within the luminal organ, thedevice is operable to detect a first conductance of a first fluid havinga first conductivity within the luminal organ using the at least twopairs of detection electrodes, the device further operable to detect asecond conductance of a second fluid having a second conductivity usingthe at least two pairs of detection electrodes upon introduction of thesecond fluid within the luminal organ at or near the at least two pairsof detection electrodes. In at least one embodiment, the second fluiddetected by using the at least two pairs of detection electrodes allowsfor the determination of flow velocity based upon timing of the detectedsecond fluid by using the at least two pairs of detection electrodes andthe distance between the at least two pairs of detection electrodes.

In at least one embodiment of a system for determining fractional flowreserve of a fluid within a luminal organ of the present disclosure, thesystem comprises a device for determining fractional flow reserve, thedevice comprising an elogated body sized and shaped to fit within aluminal organ, and at least two sensors positioned along the elongatedbody a predetermined distance from one another, wherein the device isoperable to detect a first fluid with a first parameter having a firstvalue using at least one of the at least two sensors when the device ispositioned within the luminal organ, and wherein the device is furtheroperable to detect a second fluid having a second parameter, wherein thesecond parameter of the second fluid has a second value different fromthe first value, upon introduction of the second fluid within theluminal organ at or near the at least two sensors, and a dataacquisition and processing system in communication with the device, thedata acquisition and processing system operable to calculate flowvelocity of the second fluid based upon timing of the detected secondfluid by the at least two sensors and the distance between the at leasttwo sensors.

In at least one embodiment of a system for determining fractional flowreserve of a fluid within a luminal organ of the present disclosure, thesystem comprises a device for determining fractional flow reserve, thedevice comprising an elogated body sized and shaped to fit within aluminal organ, at least one pair of excitation electrodes positionedalong the elongated body, and at least two pairs of detection electrodespositioned along the elongated body between the at least one pair ofexcitation electrodes, wherein the at least two pairs of detectionelectrodes are positioned a predetermined distance from each other,wherein when the device is positioned within the luminal organ, thedevice is operable to detect a first conductance of a first fluid havinga first conductivity within the luminal organ using the at least twopairs of detection electrodes, the device further operable to detect asecond conductance of a second fluid having a second conductivity usingthe at least two pairs of detection electrodes upon introduction of thesecond fluid within the luminal organ at or near the at least two pairsof detection electrodes, and a data acquisition and processing system incommunication with the device, the data acquisition and processingsystem operable to calculate flow velocity of the second fluid basedupon timing of the detected second fluid by using the at least two pairsof detection electrodes and the distance between the at least two pairsof detection electrodes.

In at least one embodiment of a system for determining fractional flowreserve of a fluid within a luminal organ of the present disclosure, thedata acquisition and processing system is further operable to determinefractional flow reserve when the device is positioned within the luminalorgan at or near a stenosis, wherein the fractional flow reserve isbased upon the flow velocity, a mean aortic pressure within the luminalorgan, and at least one cross-sectional area at or near the stenosis. Inanother embodiment, the flow velocity allows for the determination ofvolumetric flow based upon the flow velocity and a cross-sectional areaof the luminal organ.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows an exemplary embodiment of a portion of a device useful fordetermining flow velocity and volumetric flow comprising two sensorspositioned along a body of the device, according to the disclosure ofthe present application;

FIG. 2 shows an exemplary embodiment of a portion of a device useful fordetermining flow velocity and volumetric flow comprising a hexa-polar(six electrode) arrangement of electrodes with two outer electrodes (E)and two sets of detection electrodes (D), according to the disclosure ofthe present application;

FIG. 3A shows a graph demonstrating the increase in total conductanceover time during a transient injection of 1.5% sodium chloride solutioninto a pig coronary artery in accordance with at least one method of thedisclosure of the present application;

FIG. 313 shows a graph demonstrating the decrease in total conductanceover time during a transient injection of 0.45% sodium chloride solutioninto a pig coronary artery in accordance with at least one method of thedisclosure of the present application;

FIG. 4 shows changes in conductance over time at electrodes 1 and 2 (asshown in FIG. 2) during a 0.9% sodium chloride injection in accordancewith at least one method of the disclosure of the present application;

FIG. 5 shows an exemplary embodiment of a system useful for determiningflow velocity and volumetric flow according to the disclosure of thepresent application;

FIG. 6 shows a block diagram of a method for determining flow velocityaccording to the disclosure of the present application;

FIG. 7 shows a block diagram of a method for determining flow velocityusing impedance according to the disclosure of the present application;

FIG. 8 shows a schematic of displacement of saline by blood after theinjection of saline according to the disclosure of the presentapplication;

FIG. 9 shows a graph depicting the voltage drop across detectionelectrodes according to the disclosure of the present application;

FIG. 10 shows a schematic of isopotential field lines for a coronaryartery according to the disclosure of the present application;

FIG. 11 shows a graph showing the validation of a finite element modelaccording to the disclosure of the present application;

FIG. 12 shows a graph showing two sets of simultaneous voltage-time orconductance-time curves according to the disclosure of the presentapplication; and

FIG. 13 shows another graph showing the validation of a finite elementmodel according to the disclosure of the present application.

DETAILED DESCRIPTION

For the purposes of promoting an understanding of the principles of thepresent disclosure, reference will now be made to the embodimentsillustrated in the drawings, and specific language will be used todescribe the same. It will nevertheless be understood that no limitationof the scope of this disclosure is thereby intended.

The disclosure of the present application provides devices, systems, andmethods for determining fractional flow reserve (FFR), includingdevices, systems, and methods for determining FFR using impedance. Anexemplary method for performing the same would utilize one or moredevices (or elements/features of such a device) operable to detect achange in at least one characteristic within a vessel flow based uponthe introduction of a change to the initial flow. Such methods, anddevices and systems for performing such methods, are useful for thediagnosis of disease (including CAD) by providing accurate values forflow velocity, whereby changes in flow velocity and/or volumetric flowmay be indicative of a low or high degree of stenosis. Such changes inflow velocity and/or volumetric flow may be identified by comparing flowvelocity and/or volumetric flow at various vessels and/or organs(generally referred to as “luminal organs”) within a body, and or bycomparing flow velocity and/or volumetric flow taken at various times.

For purposes of the present application, an “indicator” shall mean asubstance introduced to, for example, a blood vessel, that includes atleast one parameter different than the native fluid flowing within sucha vessel, which may include, but is not limited to, various chemicalchanges like osmolarity and pH, for example, and/or optical, electrical,and/or thermal changes. Exemplary indicators may then be detectable by a“sensor,” which may comprise any number of applicable sensors useful todetect such indicators. Exemplary sensors may include, but are notlimited to, detection electrodes, pH sensors, thermocouples, and opticalsensors, which are operable to detect one or more indicators. A“parameter,” as referenced herein, refers to an aspect of an indicatorthat may be detected by one or more sensors, including, but not limitedto, conductivity, pH, temperature, and/or optically-detectablesubstances. The disclosure of the present application is not intended tobe limited to the specific indicators and/or sensors disclosed herein,as other indicators and/or sensors suitable for the devices, systems,and methods for determining FFR not disclosed herein may also besuitable for one or more applications of the same.

An exemplary embodiment of at least a portion of a device useful fordetermining FFR using impedance is shown in FIG. 1. As shown in FIG. 1,device 100 comprises two sensors 102 (each sensor 102 labeled “S” inFIG. 1, whereby one sensor 102 is further labeled “1” and the secondsensor 102 is further labeled “2”) positioned along the body 104 ofdevice 100 at or near the distal end of device 100. Various embodimentsof device 100 as described herein may comprise two or more sensors 102,and sensors 102 may be positioned along various portions of body 104 ofdevice 100. Additionally, device 100 may comprise any number of suitabledevices 100 with the characteristics/components described herein, whichmay include, but are not limited to, catheters and guidewires. Forexample, device 100 may comprise a standard catheter, a ballooncatheter, an angioplasty catheter, a fluid-filled silasticpressure-monitoring catheter, a standard wire, an impedance wire, aguidewire, and other catheters or wires that may include thecharacteristics of a device 100 as described herein.

In the embodiment shown in FIG. 1, sensors 102 are separated by adistance L as shown therein. As discussed in greater detail herein, anexemplary method for determining FFR is based upon the principle thattwo or more sensors 102 spaced at a predetermined distance apart can“time” the injection of a bolus injection as the plug flow moves pastthe sensors 102 sequentially (e.g., sensor 102 “1” first, and thensensor 102 “2” as shown in FIG. 1). Upon detection of the bolus bysensors 102 in accordance with the present application, a determinationof flow velocity may be determined based upon the distance between thetwo sensors 102 (L) and the time difference between the detection of thebolus by sensors 102. As previously referenced herein, such a bolus mayinclude and/or comprise one or more indicators (e.g., a hyper-osmoticsolution, a hypo-osmotic solution, a solution of a pH different from thenative fluid flowing within the target vessel, a solution of a differenttemperature than the native fluid flowing within the target vessel,etc.) detectable by sensors 102 (e.g., detection electrodes, pH sensors,thermocouples, etc.) positioned along the body 104 of device 100, sothat the indicator(s), when introduced to a vessel containing device100, are detectable at various times by the sensor(s) 102 positionedalong device 100.

In at least one embodiment of a method for determining FFR, a device 100comprising two or more sensors 102 is useful for performing said method.An exemplary method of the disclosure of the present applicationcomprises the steps of inserting such a device 100 into a vessel with afluid flow and injecting/introducing a bolus (either from said device100 or another device) which can be detected by sensors 102. In at leastone embodiment of a method 600 for determining FFR of the presentdisclosure, and as shown in the block diagram of FIG. 6, method 600comprises the step of positioning a device 100 comprising at least twosensors 102 within a vessel or organ (positioning step 602), wherein theat least two sensors 102 are separated a known distance from oneanother. Such a method 604 further comprises the steps of detecting atleast one parameter of a first fluid within the vessel or organ usingsensors 102 (first detection step 604), and injecting a second fluidhaving at least one parameter different than the at least one parameterof the first fluid into the vessel or organ to temporarily displace thefirst fluid at the site of injection (injection step 606). An exemplarymethod 600 of the present disclosure further comprises the steps ofdetecting at least the different parameter of the second fluid bysensors 102 (second detection step 608) and measuring the time ofdetection of the second fluid by each of the at least two sensors 102(measuring step 610). An exemplary method 600 may further comprise thestep of determining flow velocity of the second fluid within the vesselor organ based upon the time of detection of the second fluid by each ofthe at least two sensors 102 (flow velocity determination step 612). Anadditional exemplary method 600 of the present disclosure may furthercomprise the step of determining FFR based upon volumetric flow and across-sectional area of the vessel or organ (FFR determination step 614)as described in further detail herein.

An exemplary embodiment of at least a portion of a device useful fordetermining FFR using impedance is shown in FIG. 2. As shown theexemplary embodiment in FIG. 2, device 200 comprises at least one pairof excitation electrodes 202 (each excitation electrode 202 labeled “E”in FIG. 2) and at least two pairs of detection electrodes 204 (each pairof detection electrodes 204 labeled “D” in FIG. 2) positioned along thebody 206 of device 200 at or near the distal end of device 200. Such anarrangement of three pairs of electrodes (one pair of excitationelectrodes 202 and two pairs of detection electrodes 204) is referred toherein as a “hexa-polar” arrangement. Excitation electrodes 202, whenactivated, provide an electric field (not shown) between the excitationelectrodes 202 so that detection electrodes 204, when activated, maydetect the electric field.

Additional devices other than at least the portion of device 200 shownin FIG. 2 are also considered to be within the scope of the presentapplication. For example, an exemplary device 200 may comprise moreelectrodes than the hexa-polar arrangement of electrodes shown in FIG.2. For example, additional exemplary devices 200 may contain one pair ofexcitation electrodes 202 and three pairs of detection electrodes 204,and may further include devices 200 containing two pairs of detectionelectrodes 202 spaced a distance apart from one another so not tointerfere with the excitation field of each pair of detection electrodes202, whereby each of the two pairs of excitation electrodes 202 has atleast one pair of detection electrodes 204 positioned therebetween. Inat least one exemplary embodiment of a device 200 of the presentdisclosure, device 200 comprises one pair of excitation electrodes 202and five pairs of detection electrodes 204 spaced known distance(s)apart from one another.

As referenced above, detection electrodes 204 operate to detect aelectric field generated by a pair of excitation electrodes 202, andtherefore, at least one pair of detection electrodes 204 must bepositioned in between the pair of excitation electrodes 202 in order toproperly detect the field as referenced herein. Accordingly, and forexample, an additional embodiment of a device 200 comprising one pair ofexcitation electrodes 202 and three pairs of detection electrodes 204positioned therebetween would allow for three separate field detections,namely one detection by each of the three pairs of detection electrodes204.

An embodiment of a device 200 comprising two pairs of excitationelectrodes 202 and a pair of detection electrodes 204 positioned betweeneach pair of excitation electrodes 202 would allow each pair ofdetection electrodes 204 to each detect a field generated by each pairof excitation electrodes 202. The various embodiments referenced hereinare merely exemplary embodiments of devices 200 of the disclosure of thepresent application, and other embodiments of devices 200 are herebycontemplated within the disclosure of the present application.

Additionally, device 200 may comprise any number of suitable devices 200with the characteristics/components described herein, which may include,but are not limited to, catheters and guidewires. For example, device200 may comprise a standard catheter, a balloon catheter, an angioplastycatheter, a fluid-filled silastic pressure-monitoring catheter, astandard wire, an impedance wire, a guidewire, and other catheters orwires that may include the characteristics of a device 200 as describedherein.

Devices 100, 200 of the present disclosure may be part of a system 500as shown in the exemplary block diagram embodiment of a system fordetermining FFR using impedance of the present disclosure shown in FIG.5. As shown in FIG. 5, system 500 comprises device 100, 200 (or otherdevices in accordance with the present application) and a dataacquisition and processing system 502 in communication with the device100, 200, wherein the data acquisition and processing system 502 isoperable to calculate flow velocity of a fluid based upon the detectionof the fluid within a vessel or organ by the sensors 102 coupled todevice 100 or the detection electrodes 204 coupled to device 200. Anexemplary data acquisition and processing system 502 may comprise, forexample, a computer or another electronic device capable of receivingdata from sensors 102 or detection electrodes 204 and processing suchdata to determine flow velocity, volumetric flow, and/or FFR.

In at least one embodiment of a method for determining FFR usingimpedance, a device 200 comprising multiple excitation electrodes 202and detection electrodes 204 is useful for performing said method. Anexemplary method of the disclosure of the present application comprisesthe steps of inserting such a device 200 into a vessel with a fluid flowand injecting a bolus (either from said device 200 or another device)which can be detected by the detection electrodes 204.

In at least one embodiment of a method 700 for determining FFR usingimpedance of the present disclosure, as shown in the block diagram ofFIG. 7, method 700 comprises the steps of positioning a device 200comprising excitation electrodes 202 and at least two pairs of detectionelectrodes 204 within a vessel or organ (positioning step 702), whereinthe at least two pairs of detection electrodes 204 are separated a knowndistance from one another. The excitation electrodes 202 may then beactivated to generate an electric field detectable by the detectionelectrodes 204 (field generation step 704). Such a method 700 furthercomprises the steps of detecting the conductance of a first fluid havinga first conductivity within the vessel or organ using the detectionelectrodes 204 (first conductance detection step 706), and injecting asecond fluid having a second conductivity into the vessel or organ totemporarily displace the first fluid at the site of injection (injectionstep 708). An exemplary method 700 of the present disclosure furthercomprises the steps of detecting the conductance of the second fluid bythe at least two pairs of detection electrodes 204 (second conductancedetection step 710) and measuring the time of conductance detection byeach of the at least two pairs of detection electrodes 204 (measuringstep 712). An exemplary method 700 may further comprise the step ofdetermining flow velocity of the second fluid within the vessel or organbased upon the time of conductance detection by each of the at least twopairs of detection electrodes 204 (flow velocity detection step 714). Anadditional exemplary method 700 of the present disclosure may furthercomprise the step of determining FFR based upon volumetric flow and across-sectional area of the vessel or organ (FFR determination step 716)as described in further detail herein.

Such a method is based upon the principle that two sensors spaced atsome distance apart (for example, the two pairs of detection electrodes204 separated by a distance L as shown in FIG. 2), can time theinjection of a bolus injection as the plug flow moves past the twosensors sequentially. Upon detection of the bolus by the two pairs ofdetection electrodes 204 in accordance with the present disclosure, adetermination of flow velocity may be determined based upon the distancebetween the two detection electrodes 204, L, and the time differencebetween the detection of the bolus by the two pairs of detectionelectrodes 204.

The use of either hyper-osmotic or hypo-osmotic solution can be detectedby detection electrodes 204 as shown in FIGS. 3A and 3B, respectively.If, in accordance with the disclosure of the present application, onecombines this detection concept with a hexa-polar arrangement ofelectrodes (as shown in FIG. 2, for example) with a single injection ofeither a hyper-osmotic solution or a hypo-osmotic solution (or saline,for example, as shown in FIG. 3A), the sequential detection of thesaline solution can be made by the two sets of detection electrodes 204(labeled as “1” and “2” in FIG. 2). Accordingly, the time (t) intervalbetween the passing bolus can be determined as the difference betweenthe times detected at the two separate positions:

Δt=t ₂ −t ₁  [1]

Hence, the velocity, V, of the bolus is given by the following formula:

V=L/Δt  [2]

wherein L is the length between the sensors, and the volumetric flow isas follows:

Q=V*CSA  [3]

where cross-sectional area, CSA, may be determined using any number ofsuitable methods and/or devices for performing the same.

The equation governing the physics of electrical conductance in a bloodvessel is given by:

$\begin{matrix}{{G(t)} = {\frac{{{CSA}(t)} \cdot \sigma}{L} + {G_{p}(t)}}} & \lbrack 4\rbrack\end{matrix}$

wherein G (the conductance) is the ratio of the current induced by theexcitation electrodes 202 and the potential difference between thedetection electrodes 204, CSA is the cross-sectional area of a vessel, σis the specific conductivity of the fluid, L is the distance betweendetection electrodes 204, G_(p) is an offset error resulting fromcurrent leakage and is the effective parallel conductance of thestructure outside the vessel lumen (vessel wall and surrounding tissue),and t is the time in the cardiac cycle.

If the following is considered:

$\begin{matrix}{G_{p} = {\gamma \frac{{CSA} \cdot \sigma}{L}}} & \lbrack 5\rbrack\end{matrix}$

wherein γ is a constant, Equation [4] can be expressed as

$\begin{matrix}{G = {\frac{I}{\Delta \; V} = {\frac{{CSA} \cdot \sigma}{L}\left( {1 + \gamma} \right)}}} & \lbrack 6\rbrack\end{matrix}$

wherein I is the current through electrodes 1 and 4 (as shown in FIG. 2,for example), and ΔV is the voltage drop. The electric resistance in ablood vessel, R, is given by:

$\begin{matrix}{R = {\frac{I}{G} = {\frac{\Delta \; V}{I} = \frac{L}{{CSA} \cdot \sigma \cdot \left( {1 + \gamma} \right)}}}} & \lbrack 7\rbrack\end{matrix}$

In such an embodiment, and as referenced above, excitation electrodes202 (electrodes numbered “1” and “4” in FIG. 2) create the field andalso serve to simultaneously detect the various fluid parameters asreferenced herein.

In order to calculate the flow rate/velocity using devices 100, 200 ofthe present disclosure, a solution (such as saline, for example) isinfused into the vessel lumen over sensor 100 positioned along device100 or detection electrodes 204 positioned along device 200 aspreviously referenced therein. Pairs of excitation electrodes 202, in atleast one embodiment, are used as detectors since they are spacedfurther apart relative to detection electrodes 204, therefore providinga more accurate time of passage.

FIG. 8 shows a schematic of displacement of saline by blood after theinjection of saline. As shown in FIG. 8, the grey and black plotsrepresent the saline solution and blood in the vessel lumen,respectively, and the dashed horizontal and vertical plots represent thevessel wall and tissues surrounding the vessel segments with salinesolution and blood, respectively. Equation [7] can therefore be writtenas follows:

$\begin{matrix}\begin{matrix}{\frac{\Delta \; V_{total}}{I} = {\frac{\Delta \; V_{blood}}{I} + \frac{\Delta \; V_{saline}}{I}}} \\{= {\frac{L_{blood}}{{CSA} \cdot \sigma_{blood} \cdot \left( {1 + \gamma_{blood}} \right)} + \frac{L_{saline}}{{CSA} \cdot \sigma_{saline} \cdot \left( {1 + \gamma_{saline}} \right)}}} \\{= {\frac{L}{{CSA} \cdot \sigma_{blood} \cdot \left( {1 + \gamma_{blood}} \right)} +}} \\{{L_{saline}\begin{pmatrix}{\frac{1}{{CSA} \cdot \sigma_{saline} \cdot \left( {1 + \gamma_{saline}} \right)} -} \\\frac{1}{{CSA} \cdot \sigma_{blood} \cdot \left( {1 + \gamma_{blood}} \right)}\end{pmatrix}}}\end{matrix} & \lbrack 8\rbrack\end{matrix}$

wherein ΔV_(total) is the total voltage difference of both saline andblood interface spanning the electrodes (FIG. 8), V_(blood) is thevoltage difference of blood (right side of FIG. 8), ΔV_(saline) is thevoltage difference across saline portion (left side of FIG. 8),L_(blood) is the blood segment length, L_(saline) is the saline segmentlength, σ_(blood) is the specific conductivity of blood, σ_(saline) isthe specific conductivity of saline, γ_(blood) is a blood constant, andγ_(saline) is a saline constant. If a constant α is defined as

$\begin{matrix}{\alpha = {\frac{1}{{CSA} \cdot \sigma_{saline} \cdot \left( {1 + \gamma_{saline}} \right)} - \frac{1}{{CSA} \cdot \sigma_{blood} \cdot \left( {1 + \gamma_{blood}} \right)}}} & \lbrack 9\rbrack\end{matrix}$

then Equation [8] can be written as:

$\begin{matrix}{\frac{\Delta \; V_{total}}{I} = {\frac{\Delta \; V_{{blood}\mspace{11mu} {only}}}{I} + {\alpha \; L_{saline}}}} & \lbrack 10\rbrack\end{matrix}$

wherein ΔV_(blood only) is the voltage drop across the blood portion. Ifa constant flow rate of saline solution is assumed to flow (transport)through the vessel lumen, then

L _(saline) =v·Δt  [11]

wherein v is the mean flow velocity and Δt is the time. Equations [9]and [10] can be combined to give:

$\begin{matrix}{{\Delta \; t} = {\frac{\Delta \; V_{total}}{I \cdot \alpha \cdot v} - \frac{\Delta \; V_{{blood}\mspace{11mu} {only}}}{I \cdot \alpha \cdot v}}} & \lbrack 12\rbrack\end{matrix}$

wherein I, α, and v are constant. Hence, a linear relationship existsbetween the change in time, Δt, and the voltage difference, ΔV_(total).Prior to the injection of saline solution into the vessel segmentbetween detection electrodes 204, L_(saline)=0, Δt=0, andΔV=ΔV_(blood only). When the saline solution occupies the vessel segmentbetween detection electrodes 204, L_(saline)=L, Δt=Δt_(transport), andΔV=ΔV_(saline only).

The slope dV/dt, determined using an exemplary device 200 of the presentapplication, is shown in FIG. 9 for a typical measurement made in aswine coronary artery. FIG. 9 shows a graph depicting the electricvoltage drop across detection electrodes 204 as saline solution, forexample, displaces blood present within a vessel. A decrease in voltage,as shown in FIG. 9, implies an increase in conductance.

As shown in FIG. 9, ΔV_(blood only) and ΔV_(saline only) are measuredusing an exemplary device 200 such that

Δt _(transport) =|ΔV _(saline) ^(full) −ΔV _(blood)^(full)|/(dV/dt)  [13]

wherein Δ_(transport) is the desired Δt, ΔV_(full saline) is the voltagedrop if only saline is present (i.e., when blood is fully displaced),and ΔV_(full blood) is the voltage drop if only blood is present (i.e.,when blood washes out saline). After the velocity is determined, theflow rate in the vessel segment can be calculated according to theconservation of mass, namely

Q=CSĀ·v=CSĀ·L/Δt _(transport)  [14]

wherein Q is the volumetric flow rate, and wherein CSĀ is the mean CSAof the profile given by the mean value theorem as:

$\begin{matrix}{Q = {v\frac{\int{{CS}\overset{\_}{A}{x}}}{\int{x}}}} & \lbrack 15\rbrack\end{matrix}$

The integrals are evaluated over the profile between the proximal anddistal measurements.

As referenced herein, excitation electrodes 202 can measure the time ofpassage of the saline injection to provide the velocity since thespacing between the excitation electrodes 202 is known. The basicconcept is that a junction potential is created when the blood displacesthe injected saline, and this junction potential deflection is linear isshown below. FIG. 10 shows preliminary measurements of flow velocity inthe swine coronary artery using a flowmeter (Transonic, Inc.) and anexemplary device 200 of the present disclosure in three animals, notingthat the least-square fit shows a linear relationship with a slope of1.02 (a R² of 0.955), which is highly significant. As the CSA can bedetermined as referenced herein, the product of CSA and velocity yieldsthe desired volumetric flow rate.

A finite element model was developed to validate the linear relationshipbetween time Δt and voltage difference ΔV_(total). The equation ofcontinuity (conservation of electric charge) governing the distributionof electric potential, V, is given by Poisson's equation as

$\begin{matrix}{{\nabla{\cdot J}} = {- \frac{\partial\rho}{\partial t}}} & \lbrack 16\rbrack\end{matrix}$

where the current density, J, is related to the electric potential asJ=σ∇V and ρ, σ, and ∇ are the electric volume charge density, electricconductivity, and del operator, respectively. Equation [16] indicatesthat the electric current density diverging from a small volume per unitvolume equals to the time rate of decrease of charge per unit volume atevery point. In the present control volume, ∂ρ/∂t=0 except for specificboundaries where the driving current, I, is injected and ejected intothe control volume. Therefore, Equation [16] can be simplified as

∇·(σ∇V)=−I  [17]

The Neumann boundary condition is applied to the external boundaryexcept for the specific boundaries with the injection and ejection ofdriving current. A Galerkin finite element program was developed tocalculate the nodal electric potential as shown in the isopotentialcontour plot of the electric field for a coronary artery with bloodflows shown in FIG. 10. The isopotential field lines for a coronaryartery shown in FIG. 10 simulate the deflection of voltage when salinesolution is infused into the vessel lumen or when the saline is washedout by the blood, similar to the experimental measurements shown in FIG.9. Finally, the relationship between time Δt=L₂/v and voltage differenceΔV_(mix) was determined as represented by Equation [12]. The finiteelement model was then used to validate the linearity between Δt and ΔVas shown in FIG. 11, which shows the relationship between Δt and ΔV anda least-square fit of a perfect linear relationship (R²=1).

The flow rate may also be determined as follows. If the electrodes of anexemplary device 200 of the present disclosure are referred to as 1, 2,3 and 4 (as shown in FIG. 2), and as previously referenced herein,electrodes 1 and 4 represent excitation electrodes 202 and 2 and 3represent detection electrodes 204 useful for the detection formeasurement of diameter, for example. For velocity measurement, one canstill excite at 1 and 4, but detection is simultaneously capable with 1&2 and 3&4. This procedure provides two sets of simultaneousvoltage-time (or conductance-time) curves as the bolus passes theelectrodes as shown in FIG. 12. The shape of the curves is nearlyidentical but there is a time lag as shown in the figure.

The mean transit time for each curve can be calculated according to themean value theorem, namely

$\begin{matrix}{\overset{\_}{t} = \frac{\int{{{tG}(t)}{t}}}{G(t)}} & \lbrack 18\rbrack\end{matrix}$

wherein G(t) is the measured electrical conductance and t is the meantransit time. The difference in mean transit time (Δt) can then be usedto calculate the mean velocity since the distance between the electrodestravel by the fluid is known. When the velocity is determined asreferenced herein, the flow rate in the vessel segment can be calculatedaccording to conservation of mass as referenced in Equation [14]. Theintegrals are evaluated over the desired profile between the proximaland distal measurements.

The FFR is defined as:

$\begin{matrix}{{FFR} = \frac{P_{distal} - P_{v}}{P_{a} - P_{v}}} & \lbrack 19\rbrack\end{matrix}$

wherein P_(a) is the mean aortic pressure, P_(v) is the central venouspressure, and P_(distal) is the hyperemic coronary pressure distal tostenosis. If venous pressure is assumed to be zero or remains unchanged,Equation [19] is further simplified to:

$\begin{matrix}{{FFR} = {\frac{P_{distal}}{P_{a}} = \frac{P_{a} - {\Delta \; P}}{P_{a}}}} & \lbrack 20\rbrack\end{matrix}$

wherein ΔP is the pressure gradient along the axis of vessel segmentfrom proximal to distal portion of stenosis.

The determination of ΔP from a generated lumen profile based onconservation of momentum and energy is as follows. The Bernoulliequation (conservation of energy) is written as:

$\begin{matrix}{{\Delta \; P} = {{\frac{\rho \; Q^{2}}{2}\left( {\frac{1}{{CSA}_{distal}^{2}} - \frac{1}{{CSA}_{proximal}^{2}}} \right)} + {\sum{{energy}\mspace{14mu} {loss}}}}} & \lbrack 21\rbrack\end{matrix}$

where CSA_(proximal) and CSA_(distal) are the proximal and distalcross-sectional areas of the lumen profile obtained by an exemplarydevice 200, respectively, and Q is the flow rate through the segment asobtained above. There are two major energy losses: diffusive energy lossand energy loss due to sudden enlargement in area from greatest stenosis(minimum CSA) to normal (distal) vessel segment.

Regarding diffusive energy loss, when the flow is assumed to befully-developed in the vessel segment, the Poiseuille formula(conservation of momentum) is written as:

$\begin{matrix}{Q = {{- \frac{{CSA}^{2}}{8\; \pi \; \mu}}\frac{p}{x}}} & \lbrack 22\rbrack\end{matrix}$

wherein μ is the blood viscosity, and wherein dp/dx is the pressuregradient. Equation [22] may then be rewritten as:

$\begin{matrix}{{- {p}} = {\frac{8\; \pi \; \mu}{{CSA}^{2}}Q{x}}} & \lbrack 23\rbrack\end{matrix}$

wherein dx is the infinitesimal length of vessel. Integrating Equation[23] along the axis of vessel segment yields:

$\begin{matrix}{{\Delta \; P_{viscous}} = {\int_{0}^{L_{total}}{\frac{8\; \pi \; \mu}{{CSA}^{2}}\ Q{x}}}} & \lbrack 24\rbrack\end{matrix}$

wherein ΔP_(viscous) is the pressure drop along the axis of vesselsegment due to viscous diffusivity, and L_(total) is the length of thedistance between proximal and distal points of the profile as shown inFIG. 12.

The energy loss due to an abrupt expansion in area can be calculatedapproximately from the one-dimensional continuity, momentum and energyequations, which can be written as:

$\begin{matrix}{{\Delta \; P_{expansion}} = {\frac{\rho \; Q^{2}}{2}\left( {\frac{1}{{CSA}_{stenosis}} - \frac{1}{{CSA}_{distal}}} \right)^{2}}} & \lbrack 25\rbrack\end{matrix}$

wherein ΔP expansion is the pressure drop due to an abrupt expansion inarea, and wherein CSA_(stenosis) and CSA_(distal) are the cross-sectionareas at the stenosis and just distal to the stenosis, respectively.When Equations [24] and [26] are substituted into Equation [21], thefollowing desired result is obtained:

$\begin{matrix}{{\Delta \; P} = {{\frac{\rho \; Q^{2}}{2}\left( {\frac{1}{{CSA}_{distal}^{2}} - \frac{1}{{CSA}_{proximal}^{2}}} \right)} + {\int_{0}^{L_{total}}{\frac{8\; \pi \; \mu}{{{CSA}(x)}^{2}}Q\ {x}}} + {\frac{\rho \; Q^{2}}{2}\left( {\frac{1}{{CSA}_{stenosis}} - \frac{1}{{CSA}_{distal}}} \right)^{2}}}} & \lbrack 26\rbrack\end{matrix}$

wherein CSA_(distal) is the cross-sectional area at the distal end ofthe vessel lesion.

FIG. 13 shows a comparison of pressure drops across various stenoses(40, 50, 60, and 70% stenosis) with different lesion lengths (1, 2, and3 cm) between computational results from the finite element model basedon Equation [26], which itself can be used to determine FFR from anexemplary device 200 of the present disclosure as has been validated bya finite element simulation shown in FIG. 13.

Regarding data pressure and FFR measurements, if the flow and lesiongeometry are accurately known, the laws of physics (conservation of massand momentum) can accurately determine the pressure drop along thestenosis. A finite element simulation of actual blood vessel geometrieswas used to validate the formulation. FIG. 13 shows excellent accuracyof the physics-based equation (Equation [18]) which incorporates themeasured flow and lesion geometry as compared to a finite elementsimulation, noting that there are no empirical parameters in thisformulation, as it is strictly the geometry and flow as determined bythe devices of the present disclosure and conservation laws of physicsas referenced herein.

The disclosure of the present application, and in at least oneembodiment, uses the premise that the injection of solution tomomentarily replace the blood does not affect the normal velocity offlow through an organ. This principle has been previously validated forcontrast injections where the contrast power injection only increasedblood flow by less than 15%. It has been found that an injection rate of2-4 ml/s is substantially adequate for complete replacement of bloodwith contrast for baseline and hyperemic flow. Power injection ofcontrast into a coronary artery produces a back pressure thatmomentarily prevents blood from entering the coronary artery. Themagnitude of the generated back pressure depends on the injection rate,viscosity of injection, the ratio of vascular and aortic resistance andvessel compliance.

With the various techniques disclosed herein, and in one testingexample, flow measurements were made during contrast injection andcompleted within three seconds after the start of contrast injection. Aninjection time of three seconds was adequate to ensure that onlyundiluted contrast material was entering the vascular bed during theflow measurement time interval. As such injections do not require apower injector, changes in flow are expected to be substantially lessthan 15%, which is a well accepted clinical tolerance for such aprocedure.

While various embodiments of devices, systems, and methods fordetermining fractional flow reserve have been described in considerabledetail herein, the embodiments are merely offered by way of non-limitingexamples of the disclosure described herein. It will therefore beunderstood that various changes and modifications may be made, andequivalents may be substituted for elements thereof, without departingfrom the scope of the disclosure. Indeed, this disclosure is notintended to be exhaustive or to limit the scope of the disclosure.

Further, in describing representative embodiments, the disclosure mayhave presented a method and/or process as a particular sequence ofsteps. However, to the extent that the method or process does not relyon the particular order of steps set forth herein, the method or processshould not be limited to the particular sequence of steps described.Other sequences of steps may be possible. Therefore, the particularorder of the steps disclosed herein should not be construed aslimitations of the present disclosure. In addition, disclosure directedto a method and/or process should not be limited to the performance oftheir steps in the order written. Such sequences may be varied and stillremain within the scope of the present disclosure.

1. A method for determining a flow reserve within a luminal organ, themethod comprising the steps of: obtaining data comprising a flowvelocity of a fluid within a luminal organ, a cross-sectional area at ornear a stenosis within the luminal organ, and a pressure measurementindicative of the luminal organ, wherein the pressure measurement isdetermined using the flow velocity and the cross-sectional area withoutthe use of a pressure sensor; and determining a flow reserve of theluminal organ using the data and a data acquisition and processingsystem.
 2. The method of claim 1, wherein the step of determiningcomprises determining a fractional flow reserve.
 3. The method of claim1, wherein the flow velocity is obtained using an impedance devicepositioned within the luminal organ at or near the stenosis.
 4. Themethod of claim 1, wherein the flow velocity is obtained using animpedance device positioned within the luminal organ at or near thestenosis, the impedance device comprising at least two sensors separateda predetermined distance from one another.
 5. The method of claim 4,wherein the flow velocity is obtained by: detecting a first fluid withinthe luminal organ using at least one of the at least two sensors,wherein the first fluid has a first parameter having a first value;introducing the second fluid into the luminal organ, the second fluidtemporarily displacing the first fluid within the luminal organ at thesite of introduction, wherein the second fluid has a second parameterhaving a second value, the second value differing from the first value;detecting the second value of the second parameter of the second fluidusing the at least two sensors; measuring time of detection of thesecond value of the second parameter of the second fluid by each of theat least two sensors; and determining flow velocity of the second fluidwithin the luminal organ based upon the time of detection of the secondvalue of the second parameter of the second fluid by each of the atleast two sensors.
 6. The method of claim 5, wherein the first parameterand the second parameter are conductivity, pH, temperature, or anoptically-detectable substance.
 7. The method of claim 1, wherein thecross-sectional area is obtained from conductance data obtained using animpedance device positioned within the luminal organ at or near thestenosis.
 8. The method of claim 1, wherein the cross-sectional area isobtained from conductance data obtained using an impedance devicepositioned within the luminal organ at or near the stenosis, theconductance data obtained using (i) at least two sensors of theimpedance device separated a predetermined distance from one another,(ii) at least one additional sensor of the impedance device, or (iii) atleast one of the at least two sensors and the at least one additionalsensor.
 9. The method of claim 1, wherein the step of determining theflow reserve is further based upon a determination of volumetric flowbetween at least two sensors of an impedance device operated within theluminal organ.
 10. The method of claim 1, further comprising the stepof: diagnosing a disease based upon the determination of flow velocitywithin a luminal organ.
 11. The method of claim 1, wherein thedetermination of the flow reserve is indicative of a degree of stenosiswithin the luminal organ.
 12. A method for determining a flow reservewithin a luminal organ, the method comprising the steps of: introducingan impedance device into a lumen of a luminal organ at or near astenosis; operating the impedance device to determine a flow velocity ofa fluid within the luminal organ and to obtain conductance data usefulto determine a cross-sectional area within the luminal organ; anddetermining a pressure measurement indicative of the luminal organ,wherein the pressure measurement is determined using the flow velocityand the cross-sectional area without the use of a pressure sensor; anddetermining a flow reserve of the luminal organ using the flow velocity,the cross-sectional area, and the pressure measurement, using a dataacquisition and processing system.
 13. The method of claim 12, whereinthe step of determining comprises determining a fractional flow reserve.14. The method of claim 12, wherein the flow velocity is obtained by:detecting a first fluid within the luminal organ using at least one ofat least two sensors of the impedance device, wherein the first fluidhas a first parameter having a first value; introducing the second fluidinto the luminal organ, the second fluid temporarily displacing thefirst fluid within the luminal organ at the site of introduction,wherein the second fluid has a second parameter having a second value,the second value differing from the first value; detecting the secondvalue of the second parameter of the second fluid using the at least twosensors; measuring time of detection of the second value of the secondparameter of the second fluid by each of the at least two sensors; anddetermining flow velocity of the second fluid within the luminal organbased upon the time of detection of the second value of the secondparameter of the second fluid by each of the at least two sensors. 15.The method of claim 14, wherein the first parameter and the secondparameter are conductivity, pH, temperature, or an optically-detectablesubstance.
 16. The method of claim 12, wherein the conductance data isobtained using (i) at least two sensors of the impedance deviceseparated a predetermined distance from one another, (ii) at least oneadditional sensor of the impedance device, or (iii) at least one of theat least two sensors and the at least one additional sensor.
 17. Themethod of claim 12, wherein the step of determining the flow reserve isfurther based upon a determination of volumetric flow between at leasttwo sensors of the impedance device.
 18. The method of claim 12, furthercomprising the step of: diagnosing a disease based upon thedetermination of flow velocity within a luminal organ.
 19. The method ofclaim 12, wherein the determination of the flow reserve is indicative ofa degree of stenosis within the luminal organ.
 20. A system fordetermining a flow reserve within a luminal organ, the systemcomprising: an impedance device comprising at least two sensorsseparated a predetermined distance from one another, the impedancedevice operable to (a) determine a flow velocity of a fluid within amammalian luminal organ and (b) obtain conductance data within themammalian luminal organ useful to determine a cross-sectional area ofthe mammalian luminal organ, when at least part of the impedance deviceis positioned within the mammalian luminal organ; and a data acquisitionand processing system coupled to the impedance device, the dataacquisition and processing system configured to (a) determine thecross-sectional area using the conductance data, (b) determine apressure measurement within the mammalian luminal organ using the flowvelocity and the cross-sectional area, without the use of a pressuresensor, and (c) determine a flow reserve at or near a stenosis withinthe mammalian luminal organ using the cross-sectional area, the flowvelocity, and the pressure measurement.